Although autism is among the most highly heritable of mental disorders, its pathogenesis is poorly understood and may include environmental co-factors. Furthermore, there are no biomarkers with which to screen for disease or identify those at risk for disease. The Autism Birth Cohort (ABC) is nested within the MoBa, a Norwegian prospective, unselected, population-based pregnancy cohort (N >107,000). ASD cases are prospectively ascertained through screening of the entire MoBa population with questionnaires at 36m, 5y, 7y, and 8y, and via referrals and a national patient registry. All diagnoses are validated, and biologic samples are collected serially through pregnancy and early childhood. Implementation of early screening and diagnostic assessments provides a rich view of longitudinal trajectory and nascent signs and symptoms, and creates new opportunities to define their pathogenesis. Biologic and clinical phenotypes of ASD determined here will enable current and future generations of investigators to pursue powerful genotypic and environmental factor association analyses. Although other prospective birth cohorts track selected high risk populations, at present, the ABC is the only large cohort wherein information and samples are collected from all children and both of their parents prior to, and independent of, diagnosis and severity of disease. Biologic samples are optimized for genetic, transcriptomic, proteomic, microbiologic and toxicologic analyses. Linkage to nationwide health registries enables extensive longitudinal follow-up of the cohort at low cost. Aims include: (1) Complete, enlarge, and characterize the ABC through continued ascertainment, diagnosis, and assessment of cases of ASD (N=550-750) and age-matched controls (N=550-750); (2) Investigate: a) potential causes of, and b) early markers for ASD, including targeted examination of pre- and perinatal candidate exposures (parental age; nutrition and xenobiotics; ultrasound and assisted reproductive technologies; infection and host immunity; immunizations and other iatrogenic factors; oxidative stress responses) and heritable susceptibilities, and prospective mining of the maternal and cord blood transcriptome and proteome for ASD biomarkers; (3) Investigate trajectories of ASD and associated features (diagnostic stability, symptoms/neuroregulatory features, head circumference/somatic growth, and biological indices). Our hypothesis is that systematic, prospective, serial analyses of ABC subjects that begin in prenatal life will reveal insights into early signs and symptoms, diagnostic stability and pathogenesis that would not be otherwise obtained. PUBLIC HEALTH RELEVANCE: The reported prevalence of ASD has increased 5-1 Ox over the past 20y. Whether these disorders are truly more frequent now is controversial; nonetheless, the burden is profound in human and economic terms. Our project will exploit a large, prospective birth cohort with unique data, biologic samples and laboratory platforms to discover clues to pathogenesis, and biomarkers that will drive research and clinical management in new directions.